C3H/HeJ mice bearing i.m. transplanted KHT
sarcomas were treated with varying doses of either
1,3-bis(2-chloroethyl)-1-nitrosourea (
BCNU) or 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (
chlorozotocin;
CHLZ) as single agents or in combination with 1 mg/g of the chemical radiosensitizer,
misonidazole (MISO). Using an in vivo-in vitro tumour-excision assay, the administration of MISO simultaneously with or 3 h after low doses of
BCNU (less than 20 mg/kg) was found to give a dose-modification factor (DMF) of approximately 1.65 relative to
BCNU alone. At higher doses of
BCNU, there was less enhancement of cell kill. The DMF for tumour growth delay was likewise dependent on
BCNU dose, continuously decreasing with increasing
BCNU dose. In contrast, the anti-tumour activity of
CHLZ, assessed by both clonogenic cell survival and tumour-growth delay, was not significantly enhanced by the addition of MISO. The enhancement of gastrointestinal toxicity and haematotoxicity by
BCNU-MISO combinations was assessed by LD50/7 and CFU-S assays, respectively. MISO enhanced
BCNU marrow toxicity by
a factor of 1.2-1.3, whilst gut toxicity was enhanced by
a factor of approximately 1.2.